Study Evaluating Biomarkers In Relapsed/Refractory Pediatric Solid Tumors

NCT00106353 | Completed Phase 1 Results

• 1 other identifier: 3066K1-139
• Study Type: interventional
• Target: 71
• Locations: 7 countries
• Sites: 30

Brief Summary

This is an open label, two-part study of temsirolimus given as a 60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors. Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity. (recruiting)

Conditions

Adenocarcinoma; Neoplasms

Keywords

Pediatric Tumors

Outcome Measures

Primary Outcomes (10)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  Baseline up to End of Treatment (EOT) (within 30 days of last dose)

• Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1

  TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period.

  Baseline up to EOT (within 30 days of last dose)

• Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1

  TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period. National Cancer Institute (NCI)-graded Common Toxicity Criteria (CTC) provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).

  Baseline up to EOT (within 30 days of last dose)

• Number of Participants Who Died: Part 1

  Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).

  Baseline up to EOT (within 30 days of last dose)

• Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1

  SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability / incapacity or are a congenital anomaly or birth defect in the offspring of a study subject. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.

  Baseline up to EOT (within 30 days of last dose)

• Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1

  Temporary interruption of study treatment; may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.

  Baseline up to EOT (within 30 days of last dose)

• Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1

  Dose reduction for individual participant allowed if a dose limiting toxicity (DLT) occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of \>3 weeks) unless investigator and medical monitor agree participant should remain in the study.

  Baseline up to EOT (within 30 days of last dose)

• Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1

  Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature \>39 degrees Celsius (C), respiratory rate \>20 beats per minute (bpm), and systolic and diastolic blood pressure (BP) \>200/110 millimeters of mercury (mmHg). Participants may be reported in more than 1 category.

  Baseline up to EOT (within 30 days of last dose)

• Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1

  Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.

  Baseline up to EOT (within 30 days of last dose)

• Percentage of Participants With Objective Response (OR) at Week 12: Part 2

  Measured as Complete response (CR), Very good partial response (VGPR), or Partial response (PR) on at least 2 occasions greater than or equal to (\>=) 4 weeks apart within first 12 weeks. CR=disappearance of all primary and metastatic lesions; Homovanillic acid, Vanillymandelic acid (HVA/VMA) normal; bone marrow immunocytology negative. VGPR=disappearance of all metastatic lesions (residual areas of uptake on bone permitted); 90 to 99 percent (%) decrease in primary disease measurement; HVA/VMA normal or both decreased \>90%. PR=at least 50% decrease in primary and metastatic disease. Number of bone sites decreased by at least 50%.

  Week 12

Secondary Outcomes (28)

• Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1

  Baseline up to Month 6

• Maximum Observed Plasma Concentration (Cmax): Part 1

  0 (pre-dose), 1, 2, 6, 24, and 168 hours (hrs) post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

• Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1

  0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

• Plasma Decay Half-Life (t1/2): Part 1

  0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

• Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1

  0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Study Arms (1)

1.0

EXPERIMENTAL

Drug: Torisel

Interventions

Torisel DRUG

60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors. Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity.

Also known as: temsirolimus

1.0

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Part 1 only:
• \- Subjects with a histological diagnosis of advanced cancer (solid tumors or central nervous system \[CNS\] tumors) with disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available (histological confirmation waived for brain stem gliomas and optic pathway tumors)
• Part 2 only:
• Subjects with histologically confirmed diagnosis of refractory or relapsed: Neuroblastoma, High-grade gliomas: glioblastoma multiforme, anaplastic astrocytomas, and other high-grade gliomas (histological confirmation waived for brain stem gliomas), Rhabdomyosarcoma.
• Measurable disease (for subjects with neuroblastoma, evaluable disease as determined by a positive metaiodobenzylguanidine (MIBG) scan will also be permitted).

You may not qualify if:

• Subjects receiving enzyme-inducing anticonvulsants.
• Pulmonary hypertension or pneumonitis
• Active infection or serious intercurrent illness

Sponsors & Collaborators

• Pfizer: lead

Study Sites (30)

Pfizer Investigational Site

Birmingham, Alabama, 35233, United States

Location

Pfizer Investigational Site

San Francisco, California, 94143, United States

Location

Pfizer Investigational Site

Chicago, Illinois, 60614, United States

Location

Pfizer Investigational Site

Indianapolis, Indiana, 46202, United States

Location

Pfizer Investigational Site

Boston, Massachusetts, 02115, United States

Location

Pfizer Investigational Site

New York, New York, 10032, United States

Location

Pfizer Investigational Site

New York, New York, 11021, United States

Location

Pfizer Investigational Site

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Pfizer Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

Pfizer Investigational Site

Greenville, South Carolina, 29605, United States

Location

Pfizer Investigational Site

Memphis, Tennessee, 38105-2794, United States

Location

Pfizer Investigational Site

Houston, Texas, 77030-2399, United States

Location

Pfizer Investigational Site

Houston, Texas, 77030, United States

Location

Pfizer Investigational Site

Seattle, Washington, 98105, United States

Location

Pfizer Investigational Site

Calgary, Alberta, T3B 6A8, Canada

Location

Pfizer Investigational Site

Edmonton, Alberta, T6G 2B7, Canada

Location

Pfizer Investigational Site

Vancouver, British Columbia, V6H 3V4, Canada

Location

Pfizer Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Pfizer Investigational Site

London, Ontario, N6A 4G5, Canada

Location

Pfizer Investigational Site

Toronto, Ontario, M5G 1X8, Canada

Location

Pfizer Investigational Site

Paris, 75248, France

Location

Pfizer Investigational Site

Villejuif, 94805, France

Location

Pfizer Investigational Site

Münster, 48149, Germany

Location

Pfizer Investigational Site

Mexico City, Mexico City, 04530, Mexico

Location

Pfizer Investigational Site

Lublin, 20- 093, Poland

Location

Pfizer Investigational Site

Lublin, 20-093, Poland

Location

Pfizer Investigational Site

Warsaw, 04-730, Poland

Location

Pfizer Investigational Site

Moscow, 115478, Russia

Location

Pfizer Investigational Site

Moscow, 117513, Russia

Location

Pfizer Investigational Site

Saint Petersburg, 197110, Russia

Location

Related Publications (1)

• Geoerger B, Kieran MW, Grupp S, Perek D, Clancy J, Krygowski M, Ananthakrishnan R, Boni JP, Berkenblit A, Spunt SL. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Eur J Cancer. 2012 Jan;48(2):253-62. doi: 10.1016/j.ejca.2011.09.021. Epub 2011 Oct 25.

  PMID: 22033322 DERIVED

MeSH Terms

Conditions

Adenocarcinoma; Neoplasms

Interventions

temsirolimus

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2005
• First Posted: March 23, 2005
• Study Start: March 1, 2005
• Primary Completion: October 1, 2009
• Study Completion: January 1, 2012
• Last Updated: February 8, 2013
• Results First Posted: January 11, 2011

Record last verified: 2013-01

Locations

US (14); DE (1); ME (1); PL (3); CA (6); RU (3); FR (2)